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Effects of protein A immunoadsorption on methylglyoxal levels in patients with chronic dilated cardiomyopathy and diabetes mellitus

A. O. Doesch, S. Mueller, M. Konstandin, S. Celik, L. Frankenstein, C. Zugck, T. J. Dengler, T. Fleming, A. Bierhaus, H. A. Katus
[Applied Cardiopulmonary Pathophysiology 15: 3-13, 2011]


Objectives: The objective of this study was to investigate effects of immunoadsorption (IA) on methylglyoxal (MG) levels in patients with chronic non-familial dilated cardiomyopathy (DCM), as well as clinical and humoral markers of heart failure.
Background: Previous studies have demonstrated favourable outcomes of IA in DCM patients with diabetes mellitus (DM) and that MG sensitizes cultured cardiomyocytes to injury by post-translational modification of Thioredoxin via glycation. Therapeutic interventions scavenging advanced glycation end-products (AGE) precursors may attenuate myocardial injury in diabetic patients. Possible effects of IA on MG levels in patients with DCM and DM have never been analyzed before.
Methods: We performed IA using agarose columns on five consecutive days in 10 patients with chronic DCM and DM, congestive heart failure of NYHA class ≥ II, left ventricular ejection fraction (LVEF) ≤ 50 %, and mean time since initial diagnosis of 4.7 ± 3.9 years.
Results: Immediately after IA, IgG decreased from 10.7 ± 1.9 to 1.1 ± 0.6 g/L (89.7 %, P = 0.008) and IgG3 from 0.6 ± 0.2 to 0.2 ± 0.2 g/L (66.7 %, P = 0.01). Median NT-pro BNP was reduced from 1665.0 ng/L at baseline to 1163.0 ng/L after 6 months (P = 0.04). Also mean LVEF was significantly improved (25.5 ± 11.7 % to 30.9 ± 11.9 % after 6 months, P = 0.02) and LVEF improved ≥ 5% (absolute) in 7 of 10 (70.0 %) patients. After 6 months, bicycle spiroergometry showed a significant increase in exercise capacity from 73.3 ± 15.8 Watts to 93.3 ± 16.4 Watts (P = 0.04) while VO2max rose from 13.0 ± 2.4 to 15.0 ± 2.2 mL/min kg (P = 0.05). No significant changes in MG levels 6 months after IA (169.6 ± 56.9 nM to 208.7 ± 75.2 nM, P = 0.05) were noted.
Conclusions: In this study on patients with nonfamilial DCM and DM, IA therapy significantly improved clinical and humoral markers of heart failure severity. However, no significant changes in MG levels were observed. Therefore, these promising results in diabetic DCM patients may not be caused by altering AGE levels. Future blinded prospective multicenter studies are necessary to identify possible underlying mechanisms like polyvalent antibodies in diabetic patients.

Key words: clinical effects, diabetes mellitus, dilated cardiomyopathy, methylglyoxal, protein A immunoadsorption

Correspondence address:
Andreas O. Doesch, M.D.
Medizinische Klinik III –
Kardiologie, Angiologie, Pulmologie
Universitätsklinikum Heidelberg
Im Neuenheimer Feld 410
69120 Heidelberg
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